Water → 2-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate

HRID 1029476Notes

Reaction equation

HRID 1029476 reaction equation
[CH3:1][CH:2]([CH3:8])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].N12CCCN=C1CCCCC2.Cl[CH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:22]1[C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[N:34][C:35]([Cl:41])=[CH:36][CH:37]=2)[N:32]=1.O>CN(C)C=O.ClCCl>[CH3:1][CH:2]([CH3:8])[CH2:3][CH2:4][C:5]([O:7][CH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](=[O:30])[N:22]1[C:31]1[CH:40]=[CH:39][C:38]2[C:33](=[N:34][C:35]([Cl:41])=[CH:36][CH:37]=2)[N:32]=1)=[O:6]

Participants

7

Reactant 4

HCID 962WaterHCID 12587Isocaproic acidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 141824043-Chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone

Product 1

HCID 141824072-(7-Chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoateYield 48.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

4-Methylpentanoic acid (2.4 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (3.05 g) are added at a temperature in the region of 20° C. to a solution, maintained under an argon atmosphere, of 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)-1-isoindolinone (6.6 g) in anhydrous dimethylformamide (60 cc), and the suspension obtained is stirred for 24 hours at a temperature in the region of 20° C. Distilled water (500 cc) and dichloromethane (150 cc) are then added. The aqueous phase is separated after settling has occurred and then re-extracted with dichloromethane (2×150 cc). The organic phases are combined, washed with distilled water (3×50 cc), dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure (2.7 kPa) at 60° C. The oily residue is purified by chromatography on silica gel (150 g) contained in a column 3.5 cm in diameter [eluant: dichloromethane/methanol (98.2 by volume)]. Elution is first performed with 200 cc of solvent: the corresponding eluate is discarded; elution is then performed with 900 cc of solvent: the corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallization in ethanol, 2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxo-1-isoindolinyl 4-methylpentanoate (4 g), m.p. 147° C., is obtained.

Workup

  1. customthe suspension obtained
  2. customThe aqueous phase is separated after settling
  3. extractionre-extracted with dichloromethane (2×150 cc)
  4. washwashed with distilled water (3×50 cc)
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 60° C
  8. customThe oily residue is purified by chromatography on silica gel (150 g)
  9. washElution
  10. washelution
  11. concentrationthe corresponding eluate is concentrated to dryness under reduced pressure (2.7 kPa) at 40° C
  12. customAfter recrystallization in ethanol

Sources & evidence

ORD record
ord-53a26d1e8c9b446bac8da6ae45058760
Source dataset
uspto-grants-1992_04
Patent number
US05102890

Reaction notes

Loading…